Method of microencapsulation

ABSTRACT

A method for microencapsulation of substances is provided. The substance(s) is/are dissolved or dispersed in an organic solvent of the kind that is partially miscible in water media. This organic solution is then mixed with an aqueous solution, which is saturated with an organic solvent and an emulsifier to form an emulsion. The emulsion is then poured into water under continuous agitation for the extraction of residual solvent. The formation of the solid capsules takes place during this extraction process. The capsules are undergone to further purification, whereby the microcapsules can be separated from the water and dried. By conditions of incubation of microcapsules in water-containing formulations the wall-softening process takes place. The unique system for controlled releasing the ingredients from microcapsules is based on the above-mentioned process.

REFERENCE TO RELATED APPLICATIONS

The present application is the national stage under 35 U.S.C. §371 ofinternational application PCT/IL00/00759, filed Nov. 16, 2000, whichdesignated the United States, and which international application waspublished under PCT Article 21(2) in the English language.

FIELD OF THE INVENTION

This invention relates to a method of microencapsulation of cosmeticingredients, vitamins and pharmaceutical substances.

BACKGROUND OF THE INVENTION

Microcapsules are available usually in powder form and consist ofspherical particles, which contain an encapsulated (entrapped)substance. The spherical particle usually consists of a polymeric shelland the encapsulated active product is located within the shell. Thepolymeric shell is frequently applied as a wall-forming material, andserves as a membrane for the encapsulated substance. This membrane issemi-permeable and allows the microcapsule to be an efficient tool forcontrolled release applications.

Microencapsulation itself has various advantages. Microcapsules protectsensitive substances from degradation processes and provide means forcontrolled release of desired active substances. It also enables theconversion of liquids to powders and is used to separate substances,which are harmful upon contact with each other.

Numerous techniques for microencapsulation are available depending onthe nature of the encapsulated substance and on the type of polymerused. A widely used method for the encapsulation of water insolubledrugs within water insoluble polymers is the solvent removal method.Generally in such a process, the desired polymer is dissolved in asuitable organic solvent. This action is followed by the addition of thedesired substance to be encapsulated. This substance is either dissolvedor dispersed in the organic solvent. The resulting organicsolution/dispersion is dispersed in an aqueous phase to obtainan-oil-in-water emulsion where oily microparticles are dispersed in theaqueous phase. Upon complete removal of the solvent from themicroparticles the microcapsules are formed. Several patents describemethods of removing the solvent. U.S. Pat. No. 4,384,975 describes theremoval of the solvent by vacuum distillation. In GB 1,394,780 theremoval of the solvent is done by evaporation. In U.S. Pat. No.3,891,570 the removal of the polymer solvent is carried out by heatingthe aqueous dispersion or by reducing its pressure. In U.S. Pat. No.3,737,337 the removal of the organic solvent is done by extraction withwater, however-it is limited to certain solvent systems. U.S. Pat. No.5,916,598 describes a method for the preparation of slow-releasebiodegradable, biocompatible microparticles using the general techniqueof solvent removing, and microparticles comprising microencapsulatedactive agent.

Microencapsulation is suitable for drugs, vitamins and food supplementssince this process is easily adaptable by varying the solvents and/orthe polymers. It may yield microcapsules having desirable size, roundshape and smooth surface that are important for controlled release andfor the chemical stability of the core material.

A basic prerequisite for this process is the use of a solvent that isable to dissolve efficiently the substance to be encapsulated as well asthe wall-forming material. This solvent has to be only partially solublein water, giving rise to emulgation of an organic phase in a continuouswater phase. Chlorinated solvents such as dichloromethane, chloroform,or their mixtures with other solvents are widely used since theyfacilitate the microencapsulation process.

However all the microencapsulating technologies based on solvent systemssuch as chlorinated solvents are not applicable for food, cosmetic andpharmaceutical applications, since they do not meet FDA and otherregulations due to the presence of residual amounts of chlorinatedsolvents in the microcapsules. Simple vacuum or heat drying do notresult in a sufficiently low chlorinated solvent content so as to meetFDA regulations, thus creating an essential necessity for a method forencapsulating vitamins, food supplements, oils or pharmaceuticals by thesolvent removal technique.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide a method forencapsulating vitamins, food supplements, oils or pharmaceuticals by thesolvent removal technique, which is easily adapted to a desiredencapsulated principle.

It is a further object of the present invention to provide amicroencapsulating process by using non-chlorinated, physiologicallyacceptable solvents.

The present invention thus provides a method for the microencapsulationof a substance, comprising the stages of:

-   -   (a) dissolving or dispersing the substance together with a        wall-forming material in an organic solvent of a kind that is        partially miscible in water, to form an organic solution or        dispersion;    -   (b) mixing said organic solution or dispersion with an aqueous        solution, said aqueous solution being saturated with said        organic solvent dissolved therein and comprising an emulsifier,        to form an emulsion;    -   (c) while agitating, pouring said emulsion into water to form a    -   (d) Adding an excess amount of water to initiate extraction of        the organic solvent from the emulsion;    -   (e) incubating for a time sufficient to allow formation of        microcapsules in the mixture; and    -   (f) further removal of the residual amount of organic solvent in        said formed micrcapsules by immersing them in an alcoholic        aqueous solution.

Optionally, the mixture is further treated after stage (f) to isolatethe microcapsules. This may be done by filtration, centrifugation,washing, evaporation, liophilization, etc., as generally known per se.

In step (d) the excess amount of water is generally an excess of betweenabout 20:1 to about 50:1 (v/v).

The term “wall-forming material” used above refers to material, whichsubsequently forms a component of the external walls or layer of themicrocapsules. The wall-forming material may be a single type ofmaterial or may be a combination of the two or more different materials.The wall-forming material is typically a polymer or a combination of twoor more different polymers.

The term “partially miscible in water” should be understood as relatingto the property of being able to be dissolved in water in concentrationswhile lower than a certain critical concentration, while theconcentration thereof increases above a certain critical value, there isphase separation and the water and the organic solvents form twoseparate phases. An example of such an organic solvent is ethyl acetateor ethyl formate.

The term “saturated” should be understood as referring to a solutionthat contains the organic solvent in a concentration about the criticalvalue or slightly below, namely, a saturated solution contains aconcentration of the organic solvent close to the maximal concentrationbefore phase separation occurs. However, the term “saturated” should notbe understood in a limiting fashion in that at times, also a solutioncontaining less than 90%, and at times even about 80% of the criticalconcentration may be considered as saturated for the purpose of theinvention. The emulsifier used in stage (b) may either be a prioridissolved in the aqueous solution or may be added to the aqueoussolution simultaneously or after mixing of the organic solutiontherewith.

The term “agitation” should be understood as referring to steering,shaking, vibrating and in general to any process whereby mechanicalenergy is transferred to the liquid to cause some turbulence in theliquid.

The term “water” used in stage (c) should be understood as referringeither to pure water, or to an aqueous solution such as a salt solution.

The incubation in stage (e) is typically for 3–10 min., although it willbe understood that the invention is not limited to incubation at thistime range and that at times, incubation may be below or above theaforementioned time range.

The microcapsules produced in accordance with the invention may havedifferent, wide ranging applications, depending on the exact nature ofthe substance incorporated therein as well as on the release propertiesof the substance which is controlled by the wall-forming material whichimparts the characteristics of the microcapsules' wall. Example of usesis applied in dermal formulations, where said substance is dermalactive. As will be appreciated, the invention is not limited by theintended use of the microcapsules or the nature of the substanceencapsulated therein.

The invention also provides novel microcapsules prepared by theabove-mentioned method and those compositions comprising suchmicrocapsules.

DETAILED DESCRIPTION OF THE INVENTION

In recent years there is an increasing interest in introducing vitaminssuch as A, C, E and F (which are essentially unsaturated fatty acids)into cosmetic, dermatological, feed supplements and food additives.Vitamin C enables the growth of connective tissues and stimulatesreproduction of collagen. Vitamin E is known as an antioxidant and as ascavenger of free radicals. Vitamin A combats aging efficiently. Thus,these vitamins may be used in skin and hair care for treating phenomenonrelated to aging, pigmentation, dryness or skin disease, e.g., such aspsoriasis. These vitamins are also favorable to the restructuring of theskin. It is known that these vitamins are very unstable in solution andare sensitive to various factors, which result in their fastdecomposition and loosing of biological activity when unprotected. Theproducts of decomposition or oxidation of vitamins possess the negativebiological effects such as irritation, prooxidant activity, etc.Encapsulating these vitamins is a suitable mean for protecting themwhile retaining their biological efficacy. However, in order to besuitable for the above-mentioned use, microcapsules containing vitaminsshould not contain any remaining harmful solvents. Another importantfeature required from microcapsules is being able to effectively controlthe release of the active components from the microcapsules.

In the method proposed in the present invention all materials wererecognized by the FDA as having GRAS status, i.e. were generallyrecognized as safe. The benefit of using such materials is that thefinal product, microcapsules, are biocompatible and suitable for bothinternal and external use.

It was found by the present invention that the rapid extraction of theorganic solvent upon mixing of the organic phase with the aqueous phaseis prevented, thus leading to the formation of desired, uniformmicrocapsules. This effect is achieved by saturation of the aqueousphase with the organic solvent used for dissolving the wall-formingmaterial and the substance to be encapsulated. It appears that watersaturated with the same solvent cannot extract the solvent from theorganic phase, and thus microdroplets of organic phase have enough timeto be formed and the resulting spherical microcapsules are obtained.They are converted into hard microcapsules after slow solvent extractionby water.

The present invention affords the production of uniform microcapsulescontaining a high loading of oil soluble substances of up to 70%.

These microcapsules have spherical shape, and altering the processparameters can control smooth surface and their size from 3 to 300 μm.The microcapsules made according to the present invention can beeffectively used in topical applications due to the unique ability ofthe capsules' walls to soften and then to control release of activesubstances to target area directly. The spherical shape and the uniformsize of the microcapsules guarantee the homogenous distribution ofactive substances on the skin.

In the present invention the method of preparing the microcapsulesincludes the following stages. In the first stage, an organic solventthat is capable of dissolving or dispersing the oil soluble or the oilnon-soluble substance and the wall-forming material is chosen. Thesolvent can be selected from a variety of solvents such as ethylacetate, ethyl formate or other appropriate solvents approved by theFDA, or their mixtures. The solvent should be inactive with thedissolved material. The substance to be encapsulated by the presentprocess is then dissolved and optionally can also be dispersed in theorganic solvent to form an organic solution or dispersion. The substancecan be either a solid or a liquid. A wall-forming material is thendissolved in the organic solution/dispersion. An appropriatewall-forming polymeric material is chosen from the group ofpolyacrylates such as polyacrylic acid polymethacrylates such aspoly(methylmethacrylate), poly(n-butylmethacrylate), Eudragit RSPO,cellulose ethers such as (C₁₋₄alkyl)cellulose, or cellulose esters suchas cellulose acetate.

In the second stage an aqueous continuous phase is saturated by the sameorganic solvent (or mixture of solvents) used in the first stage. Anappropriate emulsifier is added to the aqueous phase. Such an emulsifiermay be selected from poly(vinylalcohol), sodium lauryl sulfate, laurylphosphate, ethoxylated sorbates such as Tween-80, polyglycerol andpoly(ethylene glycol), and their esters and ethers. Said addedemulsifier should be chosen and adapted to the system in such a way thatit does not separate from water after the organic solvent is added inthe next stage. It is advisable to adjust the pH of the aqueous phase tobe slightly acidic so as to prevent the hydrolysis of ethyl acetate orany other ester containing solvent.

In the third stage the organic solution/dispersion obtained in the firststage, which contains the substance and the wall-forming material, ispoured into the aqueous continuous phase saturated with the organicsolvent used in the first stage, forming an emulsion. The pouring isdone with agitation and the agitation is continued for a further periodof time. The rate of mixing and its duration affect, among otherfactors, the size of the formed droplets. Other factors, which areresponsible for the size of the formed droplets, are the ratio of waterto organic phase, temperature, quantity and kind of emulsifier.

In the fourth stage, water is added to the emulsion formed in theprevious stage, for extracting the organic solvent. Preferably, thequantity of the water added is 10–30 times higher than the wholequantity of the organic solvent in the mixture. The most preferableratio is 20:1. Following the addition of the water, the mixture isagitated for several minutes up to a point where the main amount of theorganic solvent is extracted into the water and equilibrium is reached.Typically it takes 3–10 minutes to reach equilibrium. Upon the gradualremoval of the organic solvent solid microcapsules are formed. Theformed microcapsules are then isolated by filtration or centrifugation,subsequently washed with water and dried.

Although, the FDA recognizes ethyl acetate and similar solvents as safesolvents, it is necessary sometimes to remove even trace amounts of suchsolvents (for example, because of odor).

Evaporating the solvent from the dispersion after the fourth stage (wetmicrocapsules) is not applicable for delicate and sensitive compoundssuch as used in the present invention. It should also be understood,that solvent evaporation from dried microcapsules is not effective,since diffusion of solvent through a hard polymer wall is very slow, andthe odor of the solvent may be felt even after keeping under vacuum forseveral days.

In order to remove trace amounts of the solvent the present inventionpresents a new effective extraction technique. The microcapsulesobtained after filtration are immersed in a 5% solution of ethanol inwater for 2–12 hours thereby causing the organic solvent to be extractedfrom the microcapsules. Under such conditions the organic solvent (forexample, ethyl acetate) present within the microcapsule migrates fromthe microcapsules to the outer medium rapidly, and the remaining amountof solvent in the microcapsules is well within the allowed CTFA and FDArange.

The microcapsules of the present invention, among other uses areintended for cosmetic and dermatological applications. Such a userequires a unique design of the microcapsules with respect to theirmechanical properties. While the microcapsules have to be on the onehand soft enough to rupture upon rubbing on skin they must also be hardenough on the other hand to avoid destruction of shell and realizationof the content during technological process by isolation, drying,sieving, etc.

Such mechanical properties are achieved by choosing an appropriate wallforming material. The preferred wall forming material ispoly(methyl-methacrylate) (PMMA) having a rather low molecular weightand containing 17% of free carboxylic groups. In addition, selection ofa suitable plasticizer and determining its percentage are anotherimportant factor. The plasticizer may be selected from mineral oils,silicon oils or triglycerides of fatty acids. The presence of theplasticizer in the microcapsules of the present invention affects theirmechanical properties thus positively affecting their dermal use andefficiency. This special composition enables microcapsules to remainintact during handling and become soft after 1–2 days incubating insidea cosmetic or dermatological formulation. These microcapsules may thenrupture completely upon being rubbed on skin thereby releasing theircontents.

The proposed process can effectively be used for producingdouble-layered microcapsules, where the outer layer completely andalmost uniformly covers an inner core. This technique was successfullyused for preparing microencapsulated pigments for make-up, where corecontaining, for example, brown pigment, was covered by the titaniumdioxide layer, and for masking with concurrent protection unstableand/or colored substances.

On an industrial scale production, after separation of microcapsules,the organic phase may be removed from the water phase by distillation.Thus, both the water and organic phase can be recycled.

Having generally described the invention, a further understanding can beobtained by reference to certain specific examples, which are providedherein for a purpose of illustration only and are not intended to belimiting unless otherwise specified.

EXAMPLES Example 1 A Process for Encapsulation of Oil

An aqueous phase was prepared as follow: 0.5 g of sodium lauryl sulfatewas dissolved in 50 ml of tap water saturated with 6 ml of ethylacetate. An organic phase was prepared by dissolving 0.7 g oil and 0.3 gethyl cellulose in 5 ml of ethyl acetate. The resulting organic phasewas poured into the aqueous phase while stirring and then 100 ml offresh water were added. After microcapsules were formed during a periodof about 3–10 minutes, they were filtered, washed by water and dried atthe temperature no higher 20° C. An average diameter of themicrocapsules was 70 μm. Efficiency of encapsulation reached was 99%.

Example 2 A Process for Encapsulation of Vitamin F

An aqueous phase was prepared as in example 1. The pH of the aqueousphase was further adjusted to 3 by citric acid. An organic phase wasprepared by dissolving 0.25 g vitamin F in a mixture of naturaltriglycerides of fatty acids, 0.0 μg antioxidant that can be chosen frombutylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) ortocopherol (vitamin E) and 0.74 g poly(methyl) metacrylate (PMMA) in 5ml of ethyl acetate.

The resulting organic phase was poured into the aqueous phase whilestirring and then 100 ml of fresh water were added. The resultingmicrocapsules formed were filtered, washed by water and dried at thetemperature no higher 20° C. An average diameter of the microcapsuleswas 50 μm.

Example 3 A Process for Encapsulation of Vitamin E

The preparations of the aqueous and organic phases were done in the samemanner as in example 2, vitamin E (tocopherol) rather than vitamin Fbeing dissolved in the organic phase. The resulting organic phase waspoured into the aqueous phase while stirring and then 100 ml of freshwater were added. The resulting microcapsules formed were filtered,washed by water and dried at the temperature no higher 20° C. An averagediameter of the microcapsules was 100 μm.

Example 4 A Process for Encapsulation of Vitamin A Palmitate

An aqueous phase was prepared by dissolving 0.5 g of poly(vinyl alcohol)in 50 ml water saturated by 6 ml of ethyl acetate. An organic phase wasprepared by dissolving 0.075 g retinol palmitate, 0.1 g mineral oil,0.01 g of an antioxidant (chosen from BHA, BHT, tocopherol or theirmixture) and 0.815 g PMMA in 5 ml of ethyl acetate. The organic phasewas poured into the aqueous phase while stirring and then 100 ml offresh water were added. The microcapsules formed were filtered, washedby water and dried at the temperature no higher 20° C. An averagediameter of the microcapsules was 40 μm.

Example 5 A Process for Encapsulating a Suspension of Vitamin C

An aqueous phase was prepared by saturating 100 ml water containing0.08% sodium lauryl sulphate by 12 ml ethyl acetate.

Separately an organic phase was prepared: 0.5 g of finely groundedvitamin C (particle size 5–10 micron) were added to a solution of 2 gPMMA in 10 ml ethyl acetate. After the addition, the batch was dispersedby sonication.

Organic phase was poured into the aqueous phase, and homogenated. Then400 ml of fresh water, containing 0.08% sodium lauryl sulphate wereadded for the extraction of the ethyl acetate and mixing was continuedfor several min. Formed microcapsules were separated by sedimentation,washed by water and dried.

Example 6 A Process for Encapsulation of a Mixture of Vitamins A and E

An organic phase was prepared as follows: 0.075 g vitamin A palmitate,0.25 g of vitamin E and 0.675 g of PMMA were dissolved in ethyl acetate.An aqueous phase was prepared as described in example 4. Then mixing ofphases, dilution by water, formation of microcapsules and theirisolation were done as described in example 4.

Example 7 A Process for Encapsulation of Pigments into Double-LayeredMicrocapsules.

At the first step, the inner core microcapsules were prepared asfollows. 2 g of mixed iron oxides (brown pigment) were sonicated for 1min in 8 ml of an ethyl acetate solution containing 0.25 gpoly(styrene/maleic anhydride) and 0.25 g of sodium cocoyl lactylate assurfactant. This suspension was emulgated in 100 ml 0.5% water solutionof PVA, which was preliminary saturated by ethyl acetate. This emulsionwas poured into 1000 ml fresh water during agitation to extract ethylacetate. The formed microcapsules were isolated by sedimentation,filtered and washed by fresh water.

The microcapsules obtained were immersed into 0.50 ml 5% sodiumcarbonate solution and incubated at 40° C. for one hour to enablehydrolysis of the maleic anhydride groups. This treatment is sufficientto alter the surface of the microcapsules in a way, which preventsdissolution of microcapsules in ethyl acetate at the second step ofprocess. The microcapsules were washed finally by fresh water and dried.

In the second step the microcapsules containing the brown pigment werecovered by titanium dioxide. Thus 0.8 g of titanium dioxide weresonicated in 3 ml of ethyl acetate solution of Eudragit RSPO, acopolymer of ethyl acrylate, methyl methacrylate, andtrimethylammonioummethyl methacrylate, (ROHM, Germany) and 0.1 g diethylphthalate (DEP). 0.3 g of the microcapsules containing the brown pigmentwas added to this dispersion during agitation. After a homogeneoussuspension was obtained it was poured into 50 ml of 0.5% water solutionof PVA during agitation. The obtained emulsion was poured into 500 mlfresh water, and agitated for 3 min to extract ethyl acetate. Theobtained microcapsules were isolated by sedimentation, filtered, washedby water and dried.

Under microscopic observation, microcapsules look like white separatespherical particles with smooth surface. After applying on skin, whitemicrocapsules broke down and released the brown pigment.

Example 8 A Process for Microencapsulation of Flavonoids

0.1 g of flavonoids and 1 g of titanium dioxide were suspended in 4 mlsolution of 0.2 g Eudragit RSPO (ROHM, Germany) in ethyl acetate. Thissuspension was emulgated in 50 ml water solution of PVA, saturated byethyl acetate. The resulting emulsion was poured into 500 ml of freshwater while agitating in order to extract ethyl acetate. Microcapsulesobtained were by sedimentation, filtered, washed by water and dried atthe temperature no higher 20° C. An average diameter of themicrocapsules was 100 μm.

1. A method for the production of microcapsules for dermal application,wherein the microcapsules consist of a polymer shell and a core made ofan encapsulated substance, said method comprising the steps of: (a)dissolving or dispersing the substance in an organic solvent of a kindthat is partially miscible in water and is capable of dissolving ordispersing said substance, together with a wall-forming polymericmaterial selected from the group consisting of a polyacrylate, apolymethacrylate, a cellulose ether, a cellulose ester, andpoly(styrene-co-maleic anhydride), to form an organic solution ordispersion; (b) preparing an aqueous continuous phase saturated withsaid organic solvent and comprising an emulsifier; (c) while agitating,pouring the organic solution or dispersion obtained in (a) into theaqueous continuous phase obtained in (b), to form an emulsion; (d)adding an excess amount of water to the emulsion obtained in (c) forextraction of the organic solvent from the emulsion, thus forming solidmicrocapsules; and (e) either (i) isolating the microcapsules, washingwith water, and drying at a temperature not higher than 20° C., or (ii)immersing the microcapsules in an aqueous solution of alcohol,separating the microcapsules, and drying at a temperature not higherthan 20° C.
 2. The method according to claim 1, wherein said substanceis selected from the group consisting of an oil, an oil-soluble vitamin,an oil non-soluble vitamin, a pigment, a natural extract, apharmaceutical, and mixtures thereof.
 3. The method according to claim2, wherein said oil-soluble or oil non-soluble vitamin is selected fromthe group consisting of vitamin A, B, C, D, E, F, K, and mixturesthereof.
 4. A method for the production of microcapsules for dermalapplication, wherein the microcapsules consist of a polymer shell and ancore made of an encapsulated pigment, said pigment being selected fromthe group consisting of mixed iron oxides (brown pigment), titaniumdioxide, and mixtures thereof, said method comprising the steps of: (a)dispersing the pigment in an organic solvent of a kind that is partiallymiscible with water and is capable of dissolving or dispersing saidpigment, together with a wall-forming polymeric material selected fromthe group consisting of a polyacrylate, a polymethacrylate, a celluloseether, a cellulose ester, and poly(styrene-co-maleic anhydride), to forman organic solution or dispersion; (b) preparing an aqueous continuousphase saturated with said organic solvent and comprising an emulsifier;(c) while agitating, pouring the organic dispersion obtained in (a) intothe aqueous continuous phase obtained in (b), to form an emulsion; (d)while agitating, adding an excess amount of water to the emulsionobtained in (c) for extraction of the organic solvent from the emulsion,thus forming solid microcapsules; and (e) either (i) isolating themicrocapsules, washing with water, and drying at a temperature nothigher than 20° C., or (ii) immersing the microcapsules in an aqueoussolution of alcohol, separating the microcapsules, and drying at atemperature not higher than 20° C.
 5. The method according to claim 2,wherein said substance is at least one flavonoid.
 6. The methodaccording to claim 1, wherein said organic solvent partially misciblewith water is an organic solvent approved for dermatologicalapplication.
 7. The method according to claim 6, wherein said organicsolvent is selected from the group consisting of ethyl acetate, ethylformate, and mixtures thereof.
 8. The method according to claim 1,wherein said polymethacrylate is selected from the group consisting ofpoly(methylmethacrylate), poly(n-butylmethacrylate) and a copolymer ofethyl acrylate, methyl methacrylate and trimethylammoniummethylmethacrylate.
 9. The method according to claim 1, wherein saidemulsifier of step (b) is selected from the group consisting ofpolyvinyl alcohol, sodium lauryl sulfate, lauryl phosphate, sodiumcocoyl lactylate, an ethoxylated sorbate, polyglycerol, poly(ethyleneglycol), and their esters and ethers.
 10. The method according to claim1, wherein the amount of added water in step (d) is 10–30 times higherthan the whole quantity of the organic solvent in the mixture,optionally at the ratio of 20:1.
 11. The method according to claim 1,wherein in step (e)(ii) the microcapsules are immersed in an aqueoussolution of alcohol consisting of a 5% solution of ethanol in water, for2–12 hours.
 12. Microcapsules consisting of a polymer shell and a coremade of an encapsulated substance for cosmetic and dermatologicalapplications, wherein said microcapsules are obtained according to amethod comprising the steps of: (a) dissolving or dispersing thesubstance in an organic solvent of a kind that is partially misciblewith water and is capable of dissolving or dispersing said substance,together with a wall-forming polymeric material selected from the groupconsisting of a polyacrylate, a polymethacrylate, a cellulose ether, acellulose ester, and poly(styrene-co-maleic anhydride), to form anorganic solution or dispersion; (b) preparing an aqueous continuousphase saturated with said organic solvent and comprising an emulsifier;(c) while agitating, pouring the organic solution or dispersion obtainedin (a) into the aqueous continuous phase obtained in (b), to form anemulsion; (d) adding an excess amount of water to the emulsion obtainedin (c) for extraction of the organic solvent from the emulsion, thusforming solid microcapsules; and (e) either (i) isolating themicrocapsules, washing with water, and drying at a temperature nothigher than 20° C., or (ii) immersing the microcapsules in an aqueoussolution of alcohol, separating the microcapsules, and drying at atemperature not higher than 20° C.
 13. Microcapsules according to claim12 which are soft enough to rupture upon rubbing on the skin therebyreleasing their contents but hard enough to remain intact and avoidrelease of their contents during isolation, drying and sieving carriedout in step (e).
 14. Microcapsules according to claim 12, furthercomprising a plasticizer.
 15. Microcapsules consisting of a polymershell and a core made of an encapsulated substance for cosmetic anddermatological applications, obtained according to a method comprisingthe steps of: (a) dissolving or dispersing the substance in an organicsolvent of a kind that is partially miscible with water and is capableof dissolving or dispersing said substance, together with a wall-formingpolymeric material selected from the group consisting of a polyacrylate,a polymethacrylate, a cellulose ether, a cellulose ester, andpoly(styrene-co-maleic anhydride), to form an organic solution ordispersion; (b) preparing an aqueous continuous phase saturated withsaid organic solvent and comprising an emulsifier; (c) while agitating,pouring the organic solution or dispersion obtained in (a) into theaqueous continuous phase obtained in (b), to form an emulsion; (d)adding an excess amount of water to the emulsion obtained in (c) forextraction of the organic solvent from the emulsion, thus forming solidmicrocapsules; and (e) either (i) isolating the microcapsules, washingwith water, and drying at a temperature not higher than 20° C., or (ii)immersing the microcapsules in an aqueous solution of alcohol,separating the microcapsules, and drying at a temperature not higherthan 20° C., said microcapsules further comprising a plasticizer,wherein said plasticizer is selected from the group consisting ofmineral oils, silicon oils and triglycerides of fatty acids. 16.Microcapsules for cosmetic and dermatological applications, which aredouble-layered microcapsules, where the outer layer completely andalmost covers an inner core consisting of a polymer shell and a coremade of an encapsulated substance, wherein said double-layeredmicrocapsules are obtained according to a method comprising the stepsof: (a) dissolving or dispersing the substance in an organic solvent ofa kind that is partially miscible with water and is capable ofdissolving or dispersing said substance, together with a wall-formingpolymeric material selected from the group consisting of a polyacrylate,a polymethacrylate, a cellulose ether, a cellulose ester, andpoly(styrene-co-maleic anhydride), to form an organic solution ordispersion; (b) preparing an aqueous continuous phase saturated withsaid organic solvent and comprising an emulsifier; (c) while agitating,pouring the organic solution or dispersion obtained in (a) into theaqueous continuous phase obtained in (b), to form an emulsion; (d) whileagitating, adding an excess amount of water to the emulsion obtained in(c) for extraction of the organic solvent from the emulsion, thusforming solid microcapsules; (e) either (i) isolating the microcapsules,washing with water, and drying at a temperature not higher than 20° C.,or ii) immersing the microcapsules in an aqueous solution of alcohol,separating the microcapsules, and drying at a temperature not higherthan 20° C.; and (f) covering the microcapsules with an outer layer byrepeating steps (a) to (e) with a second substance, thus obtaining thedouble-layered microcapsules, where the outer layer completely andalmost covers an inner core consisting of a polymer shell and a coremade of an encapsulated substance.
 17. Double-layered microcapsulesaccording to claim 16 comprising pigments for make-up, wherein an innercore of brown pigment is covered by a titanium dioxide layer. 18.Composition for skin care, skin supplement or sun care comprisingmicrocapsules according to claim
 12. 19. Composition comprisingmicrocapsules according to claim 12 wherein the encapsulated substanceis a color cosmetic or a cosmeticeutical.
 20. Composition for oralhygiene or oral care comprising microcapsules according to claim 12.